Methods for protecting the brain and other tissues from virus-associated toxicity are provided. Patients are treated with a first immunizing virus prior to administration of a second, therapeutic cytolytic virus. The immunizing virus is preferably administered peripherally, and initiates an adaptive immune response that is sufficient to reduce or prevent the cytovirulence and inflammation caused by the therapeutic virus. The immunizing virus is administered one or more times, preferably at least twice, before administration of the therapeutic virus. The therapeutic virus can be the same virus as the immunizing virus, or a mutant or variant thereof. Preferably the therapeutic virus is an attenuated virus with reduced virulence compared to the immunizing virus.
